Biomimetic amphiphilic chitosan nanoparticles: Synthesis, characterization and antimicrobial activity

Naturally derived antimicrobial peptides (AMPs) are an attractive source of new antimicrobial agents. However, clinical application of AMPs is associated with poor bioavailability and toxicity. In this study, we address these limitations by designing a new series of chitosan derivatives to mimic the amphiphilic topology of AMPs. The synthesized chitosan derivatives were found to self-assemble into nanoparticles in the aqueous environment. Among the compounds, a chitosan derivative grafted with arginine and oleic acid (CH-Arg-OA) exhibited the most potent antimicrobial activity, especially against Gram-negative bacteria. It also caused minimal cell death when tested in HEK293 and HepG2 cell lines, thus confirming the role of cationicity and lipophilicity for selective bacteria targeting. CH-Arg-OA exhibited its antimicrobial activity by disrupting bacterial membranes and causing the leakage of cytoplasmic contents. Thus, amphiphilic chitosan nanoparticles offer a great promise as a new class of AMPs mimics that is effective against Gram-negative bacteria.

Automated summary

Natural antimicrobial peptides (AMPs) are a promising source for new antimicrobial agents, but their clinical application is limited by poor bioavailability and toxicity. This study addresses these limitations by designing a new series of chitosan derivatives that mimic the structure of AMPs, with one derivative showing the most potent antimicrobial activity against Gram-negative bacteria while causing minimal cell death in tested cell lines. The results confirm the importance of cationicity and lipophilicity for selective bacteria targeting with the potential for chitosan nanoparticles as a new class of AMPs mimics effective against Gram-negative bacteria.